Saturday, 21 August 2010

The main request before the Board was found not to comply with the requirements of A 123(2).

Claim 1 of auxiliary request I read:

A solid composition comprising

(a) a drug in a pharmaceutically acceptable solubility-improved form selected from a crystalline highly soluble salt form of the drug, a high-energy crystalline form of the drug, a hydrate or solvate crystalline form of the drug, an amorphous form of the drug, a mixture of the drug with a solubilizing agent; and

[5] Having regard to the written submissions on file and the outcome of the oral proceedings, there is no evidence that the person skilled in the art per se would know which level of solubility-improvement a drug has to fulfil to be classified “solubility-improved”. This lack of evidence in particular applies to a hydrate or solvate crystalline form of the drug or to an amorphous form of the drug, and is also relevant with respect to the question as to when a crystalline soluble salt is to be called a crystalline highly soluble salt.

Consequently, the skilled reader of the application in suit is bound to particular definitions within this application in order to be able to clarify the subject- matter of solubility-improved drugs or “crystalline highly soluble salt” forms.

The application in suit contains an effort to give an exact definition on page 31, lines 20 to 25. “Preferred highly soluble salt forms” are defined as “those salt forms that have aqueous solubility at least 1.25-fold, preferably at least 2-fold, and more preferably at least 5-fold, the aqueous solubility of the more soluble of the crystalline free base and the crystalline hydrochloride salt forms”.

But as the facts on file stand, this attempt to define the term “solubility-improved” relates only to particular cases not referred to in the current requests and therefore is of no general use.

With respect to a hydrate or solvate crystalline form as contained in auxiliary request I, there is no definition to be found at all, while as far as “an amorphous form of the drug” is concerned, the skilled person finds that he has to compare in at least an in vitro test medium a maximum concentration of the drug to the equilibrium concentration of the drug provided by the drug in crystalline form. However, in this case it is not clear what crystalline form is meant; it could be exactly the purely crystalline form of the same salt as the amorphous form that is tested, or the crystalline form of the lowest solubility form of the drug itself, whether salt or not or anything else.

Consequently, with the definition either missing altogether or based on a comparison to an undefined reference with respect to a hydrate or solvate crystalline form of the drug or to an amorphous form of the drug, the feature of the solubility-improved drug form has to be regarded as unclear under A 84 in auxiliary request I.

The Board then turns to auxiliary request II. The single claim of this request read:

A composition comprising

(a) a drug in a pharmaceutically acceptable solubility-improved form being a crystalline highly soluble salt form of the drug; and

[6] In the case of “crystalline highly soluble salts” there is a definition in the description that tells the skilled person to compare in at least one in vitro test medium the maximum concentration of the drug to the equilibrium concentration provided by the lowest solubility form of the drug […] which may be measured as indicated in the examples given.

He can work this out in the framework of reproducibility or repeatability of measurements, even if he will find that this condition is met by nearly all forms of a drug except the only one that is the lowest solubility form. The term “lowest solubility form of the drug” is to be understood with respect to the state of the art at the priority date of the application […].

Thus, this feature is the basis for a very broad claim, but it is at least clear under A 84.

The case was then remitted to the first instance for further prosecution.

Should you wish to download the whole decision (T 1638/06), just click here.

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